This research proposal is designed as a systematic interdisciplinary study to test the hypotheses that bulbospinal norepinephrine (NE) and serotonin (5-HT) pathways that terminate in the intermediolateral columns of the spinal cord provide, respectively, excitatory and inhibitory influences on the excitability of sympathetic preganglionic neurons and are functionally important in the central regulation of blood pressure. A closely related study is directed toward discriminating between spinal and medullary sites of action of centrally acting antihypertensive drugs and determining mechanisms of action at the spinal site. Established electrophysiological technics are coupled with selective neuropharmacological manipulation to obtain comprehensive information about the neuroanatomy, function, neurochemistry, and neuropharmacology of monoaminergic and other bulbospinal sympathetic pathways. Histological identification and neurochemical assay are included to obtain definitive supporting information. Experiments rely heavily but not exclusively upon on-line analysis of readily quantifiable sympathetic discharges recorded from sympathetic preganglionic white rami and evoked by single-pulse stimulation of several afferent and efferent pathways in the brainstem and spinal cord of anesthetized or spinal cats. Several approaches are used to provide results that are mutually complementary or discriminatory. This project is divided into three Phases: 1. Functional neuroanatomy, 2. Neurochemistry and neuropharmacology, and 3. Centrally acting antihypertensives. This research will provide new comprehensive information on bulbospinal sympathetic pathways that should contribute to further understanding of the etiology and treatment of essential and other forms of hypertension and of the control of blood pressure by the central nervous system.